Lung cancer is the leading cause of cancer death worldwide. In the United States, its incidence rate is the second highest among men and women and is the most common cause of cancer death in both sexes. Similar data are found in Europe, where lung cancer is the third most common cancer and is the leading caused of cancer death. Smoking tobacco is the major risk factor for lung cancer. It is estimated that about 90% of lung cancer deaths are due to smoking.
Lung cancer comprises two main histological subtypes: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). The latter accounts for 80-85% of all cases and includes the two most frequent lung cancer types: adenocarcinomas and squamous cell carcinomas.
Irrespective of the histology, lung cancer is often detected at advanced stages, when the disease is almost incurable. This explains the poor five-year survival rate, which rounds 15-20% for all lung cancer tumors, and is less than 5% in metastatic cases. A lack of effective techniques for early detection is one of the main reasons behind these dismal statistics. Nowadays, less than 20% of patients are diagnosed in early stages, when surgical intervention is possible; in consequence, extensive efforts are devoted to significantly increase the percentage of early detected cases.
In the last years, low-dose circular tomography (CT)-based lung cancer screening studies have reported high rates of detection of small cancers in early stages (Henschke C. I. et al, 2006). A study including more than 50,000 participants (Aberle D. R. et al., 2011) concluded that screening with the use of spiral CT detects lung tumors at early stages (mostly stage I) and reduces mortality from lung cancer. However, to be really efficacious in population-based screening programs, high levels of sensitivity and specificity are needed. In this respect, especially interesting is the possibility of combining radiological techniques with the use of molecular markers which may select those individuals who are at higher risk of developing cancer in their lungs. Moreover, these biomarkers may help to confirm the presence of malignant cells and predict its evolution and its biological response to treatment. In particular, in CT-based lung cancer screening protocols, biomarkers may be very helpful to discriminate which of the nodules found by imaging may lead to more aggressive tumors and need more active follow up. Unfortunately, in spite of the efforts made, the search for molecular biomarkers for lung cancer has had a very limited success and, at present, there are not molecular markers available that can be routinely used for risk assessment, diagnosis, prognosis, or monitoring of treatment in lung cancer.
Some studies have suggested that the complement system is activated in patients with neoplastic diseases. In the case of lung cancer, there are contradictory results. Immunohistochemical analysis revealed a minimal deposition of C3b (a component of the alternative complement system) with an apparent lack of activation of the lytic MAC (Niehans G. A. et al., 1996). However, elevated complement levels correlating with tumor size were found in lung cancer patients (Nishioka K. et al., 1976), and complement components C3c and C4 were significantly elevated in patients with lung cancer when compared with a control group. Many proteomic studies have also reported an elevation of complement components in the plasma of lung cancer patients (Oner F. et al, 2004). It has also been disclosed that the classical complement pathway is not activated in patients suffering from lung cancer because no reduction in the levels of C4 was detected (Hou et al., 1985).
In conclusion, at present, there are not molecular markers available that can be routinely used for risk assessment, diagnosis, prognosis, or monitoring of treatment in lung cancer.